Premium
A systematic association mapping on chromosome 6q in bipolar affective disorder—evidence for the melanin‐concentrating‐hormone‐receptor‐2 gene as a risk factor for bipolar affective disorder
Author(s) -
Abou Jamra Rami,
Schulze Thomas G.,
Becker Tim,
Brockschmidt Felix F.,
Green Elaine,
Alblas Margrieta A.,
Wendland Jens R.,
Adli Mazda,
Grozeva Detelina,
Strohmeier Jana,
Georgi Alexander,
Craddock Nick,
Propping Peter,
Rietschel Marcella,
Nöthen Markus M.,
Cichon Sven,
Schumacher Johannes
Publication year - 2010
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31051
Subject(s) - bipolar disorder , association (psychology) , psychology , clinical psychology , psychiatry , medicine , psychotherapist , mood
Strong evidence of linkage between chromosomal region 6q16‐q22 and bipolar affective disorder (BPAD) has previously been reported. We conducted a systematic association mapping of the 6q‐linkage interval using 617 SNP markers in a BPAD case–control sample of German descent (cases = 330, controls = 325). In this screening step, 46 SNPs showed nominally significant BPAD‐association ( P ‐values between 0.0007 and 0.0484). Although none of the 46 SNPs survived correction for multiple testing, they were genotyped in a second and ethnically matched BPAD sample (cases = 328, controls = 397). At the melanin‐concentrating‐hormone‐receptor‐2 ( MCHR2 ) gene, we found nominal association in both the initial and second BPAD samples (combined P = 0.008). This finding was followed up by the genotyping of 17 additional MCHR2 ‐SNPs in the combined sample in order to define our findings more precisely. We found that the MCHR2 ‐locus can be divided into three different haplotype‐blocks, and observed that the MCHR2 ‐association was most pronounced in BPAD male patients with psychotic symptoms. In two neighboring blocks, putative risk‐haplotypes were found to be 7% more frequent in patients (block II: 23.3% vs. 16.2%, P = 0.005, block III: 39.2% vs. 32.0%, P = 0.024), whereas the putative protective haplotypes were found to be 5–8% less frequent in patients (block II: 11.6% vs. 16.4%, P = 0.041, block III: 30.0% vs. 38.8%, P = 0.007). The corresponding odds ratios (single‐marker analysis) ranged between 1.25 and 1.46. Our findings may indicate that MCHR2 is a putative risk factor for BPAD. These findings should be interpreted with caution and replicated in independent BPAD samples. © 2009 Wiley‐Liss, Inc.